Comparing Efficacy and Safety of Insulin Detemir Plus Insulin Aspart and NPH Insulin Plus Human Soluble Insulin With or Without Metformin in Chinese Patients With Type 2 Diabetes

A 2-week, Randomised, Controlled, Open-label, Two-group Parallel, Multi-centre Trial Comparing Efficacy and Safety of Insulin Detemir Plus Insulin Aspart and NPH Insulin Plus Human Soluble Insulin Both in a Basal Bolus Regimen With or Without Metformin in Chinese Inpatients With Type 2 Diabetes Currently Treated With Insulin Qualifying for Intensified Treatment

This trial is conducted in Asia. The aim of this trial is to compare efficacy and safety of insulin detemir plus insulin aspart and NPH insulin plus human soluble insulin both in a basal bolus regimen with or without metformin in Chinese patients with type 2 diabetes.

The trial adopts a group sequential design, where the analysis of the primary efficacy endpoint will be performed at the interim analysis, in addition to the final formal analysis. The decision to continue or stop the trial will be based on the result of the interim analysis.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: insulin detemir; Drug: insulin aspart; Drug: metformin; Drug: insulin NPH; Drug: human soluble insulin

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Novo Nordisk Investigational Site
  • Chongqing
    • Chongqing, Chongqing, China, 400016
      • Novo Nordisk Investigational Site
  • Jiangsu
    • Wuxi, Jiangsu, China, 214023
      • Novo Nordisk Investigational Site
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Novo Nordisk Investigational Site
  • Shanghai
    • Shanghai, Shanghai, China, 200003
      • Novo Nordisk Investigational Site
    • Shanghai, Shanghai, China, 200072
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 2 diabetes mellitus (diagnosed clinically) for at 12 months or longer
• Currently treated with basal insulin once daily or premixed insulin twice daily for at least 3 months with or without OAD(s), and total daily insulin dose less than 1.4 IU (U)/kg (If treated with metformin, unchanged total daily dose of at least 1000 mg for at least 3 months)
• Body Mass Index (BMI) equal to 40 kg/m^2 or below
• HbA1c (glycosylated haemoglobin A1c) between 7.0% and 10.0% by central laboratory analysis
• Plan to be admitted for optimising glycaemic control at least 2 days prior to the randomisation

Exclusion Criteria:

• Treatment with thiazolidinediones (TZD) or Glucagon-Like Peptide-1 (GLP-1) receptor agonists within the last 3 months prior to the screening
• Anticipated change after the randomisation in concomitant medication known to interfere with glucose metabolism, such as systemic corticosteroids, beta-blockers and mono amine oxidase (MAO) inhibitors
• Previous participation in this trial (participation is defined as randomised. Re-screening of screening failures is allowed only once within the limits of the recruitment period.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin detemir / IAsp	Drug: insulin detemir; Dose individually adjusted. Administered subcutaneously/s.c. (under the skin) once daily using NovoPen®4; Drug: insulin aspart; Dose individually adjusted. Administered subcutaneously/s.c. (under the skin) three times a day before a meal using NovoPen®4; Drug: metformin; For subjects previously treated with metformin, the dosage and frequency will be kept unchanged
Active Comparator: insulin NPH	Drug: metformin; For subjects previously treated with metformin, the dosage and frequency will be kept unchanged; Drug: insulin NPH; Dose individually adjusted. Administered subcutaneously/s.c. (under the skin) once daily using NovoPen®4; Drug: human soluble insulin; Dose individually adjusted. Administered subcutaneously/s.c. (under the skin) three times a day before a meal using NovoPen®4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean 8-point Plasma Glucose (PG) After Two Weeks of Treatment	Mean value of 8-point PG was the arithmetic mean of all 8 time-instant PG values of the 8-point PG profile.	Week 0, week 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Fasting Plasma Glucose (FPG) After Two Weeks of Treatment	The FPG referred to pre-breakfast plasma glucose.	Week 0, week 2
Change From Baseline in Mean 2-hour Post Prandial Plasma Glucose (2hPPG) of 3 Meals After Two Weeks of Treatment	The mean 2hPPG was derived from the 8-point PG profile as the mean value of the available 120 minutes after each meal.	Week 0, week 2
Change From Baseline in Mean Value of Pre-lunch, Pre-dinner and Bedtime PG After Two Weeks of Treatment	The mean value of pre-lunch, pre-dinner and bedtime PG was derived from the 8-point PG profile measured before lunch, dinner and bedtime.	Week 0, week 2
Percentage of Subjects Achieving FPG < 6.0 mmol / L After Two Weeks of Treatment		Week 2
Percentage of Subjects Achieving Mean 2hPPG of 3 Meals < 8.0 mmol / L After Two Weeks of Treatment		Week 2
Percentage of Subjects Achieving Both FPG and 2hPPG Targets After Two Weeks of Treatment	FPG target was < 6.0 mmol / L, 2hPPG target was < 8.0 mmol / L.	Week 2
Percentage of Subjects Achieving FPG Target Without Nocturnal Hypoglycaemia After Two Weeks of Treatment	FPG target was < 6.0 mmol / L. Nocturnal hypoglycaemia was defined as a hypoglycaemic episode happened between 00:01 and 05:59 a.m. (both included).	Week 2
Change From Baseline in Fructosamine After Two Weeks of Treatment		Week 0, week 2
Incidence of Hypoglycaemic Episodes	All events summarized were treatment emergent hypoglycaemic events. Hypoglycaemic episodes were summarized based on the ADA classification and also according to an additional definition. Severe hypoglycemia: ADA definition. Minor hypoglycaemic episode: an episode with symptoms with confirmation by plasma glucose (PG) < 3.1 mmol/l (56 mg/dl) and was handled by the subject himself/herself, or any asymptomatic PG value < 3.1 mmol/l (56 mg/dl). A hypoglycaemia episode was defined as nocturnal if the time of onset was between 00:01 and 05:59 a.m. (both included), otherwise it was diurnal.	Weeks 0-2

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Guo X, Li Q, Shi Y, Bu R, Liu J, Qu S, Gao Y. Efficacy and safety of insulin detemir plus insulin aspart versus NPH insulin plus human soluble insulin with or without metformin in Chinese type 2 diabetes. Chinese J Diabetes 2014; 22 (1)

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: December 5, 2011
• First Submitted That Met QC Criteria: December 6, 2011
• First Posted (Estimate): December 7, 2011

Study Record Updates

• Last Update Posted (Actual): March 17, 2017
• Last Update Submitted That Met QC Criteria: February 9, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Aspart; Metformin; Insulin Detemir; Insulin, Isophane; Isophane Insulin, Human; Isophane insulin, beef
• Other Study ID Numbers: NN304-3954; U1111-1123-7088 (Other Identifier: WHO)